54例复治利福平耐药结核病患者菌株遗传特征及耐多药基因分析OACSTPCD
Analysis of genetic characteristics of MTB and multi-drug resistance genes of 54 retreated rifampicin-resistant tuberculosis patients
目的 分析54例复治利福平耐药结核病(RR-TB)患者的结核分枝杆菌(MTB)菌株遗传特征及耐多药基因突变情况.方法 选择同时留存有初治及复治MTB菌株的复治RR-TB患者54例,取其初治及复治时的MTB共54对(108株),采用RD105基因缺失法检测其基因型,15位点可变数目串联重复序列基因分型实验(MIRU-VNTR)判断其复治发病原因;取复治时的MTB 54株,通过MIRU-VNTR结果构建最小生成树(MST),分析群体遗传特征;采用分子线性探针药敏实验分析复治MTB的耐多药基因(利福平耐药rpoB基因及异烟肼耐药katG、inhA基因)突变情况.结果 108株复治RR-TB患者的MTB均为北京基因型,内源性复燃占比77.8%(42/54)、外源性再感染占比22.2%(12/54).MST显示,54株复治MTB分为3个克隆复合群(CC1、CC2、CC3)和13个独特基因型;共48种基因型,成簇率为11.1%.分子线性探针药敏试验结果显示,异烟肼耐药katG、inhA基因突变40株,耐多药率为74.1%(40/54);利福平耐药rpoB基因以S531L位点突变为主(63.0%,34/54),异烟肼耐药katG基因以S315T1位点突变为主(75.0%,30/40).结论 北京地区复治RR-TB患者发病原因主要是内源性复燃,主要流行菌株为北京基因型,呈现出较高的遗传多样性,成簇率较低,MTB耐多药基因突变位点多为rpoB基因S531L及katG基因S315T1.
Objective To analyze the genetic characteristics of Mycobacterium tuberculosis(MTB)strains and drug resistance gene mutations in 54 cases of retreated rifampicin-resistant tuberculosis(RR-TB)patients.Methods Fifty-four retreated RR-TB patients who retained both initial and recurrent MTB strains were included in the study.A total of 54 pairs(108 strains)of MTB were collected at the time of initial and recurrent treatment,and their genotypes were detected by RD105 gene deletion method.15-locus variable number tandem repeat genotyping experiment(MIRU-VNTR)was used to determine the cause of the recurrent disease.We constructed a minimum spanning tree(MST)based on the MIRU-VNTR results of 54 cases of recurrent MTB,and analyzed the genetic characteristics of the strains.Molecular linear probe assay was used to analyze the mutations of rifampicin-resistant rpoB gene and isoniazid-resistant katG and inhA genes in re-treated RR-TB strains.Results All 108 MTB strains from the patients with retreated RR-TB were Beijing genotype.The proportion of endogenous reactivation in retreated RR-TB patients was 77.8%(42/54),while the proportion of exogenous reinfection was 22.2%(12/54).MST showed that 54 retreated RR-TB strains were divided into 3 clone complexes(CC1,CC2,CC3)and 13 unique genotypes;they had 48 genotypes in total,with a clustering rate of 11.1%.Molecular linear probe assay showed that there were 40 cases of mutations in the isoniazid-resistance genes katG and inhA,with a multidrug resistance rate of 74.1%(40/54).The rifampicin-resistant rpoB gene was mainly mutated at the S531L site(63.0%,34/54),while the isoniazid-resistant katG gene was mainly mutated at the S315T1 site(75.0%,30/40).Conclusions En-dogenous reactivation was the main cause of retreated RR-TB patients in Beijing area.The predominant strain was the Bei-jing genotype,showing high genetic diversity and low clustering rate.Most of the multidrug-resistant gene mutation sites were rpoB gene S531L site and katG gene S315T1 site.
张洁;任怡宣;杨新宇;田丽丽;易俊莉;丁北川
北京市疾病预防控制中心,北京 100013
临床医学
结核分枝杆菌结核病内源性复燃耐药基因利福平异烟肼
Mycobacterium tuberculosistuberculosisendogenous reactivationdrug resistance generifampi-cinisoniazide
《山东医药》 2024 (011)
27-30,35 / 5
首都卫生发展科研专项(首发2020-2-1042).
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